Allergic Rhinitis Clinical Trial
— UBAMBIOfficial title:
Determination of Threshold Concentrations for Ragweed and Birch Pollen in Sensitized Patients With Seasonal Allergic Rhinitis in an Allergen Challenge Chamber and in Vitro
The ragweed Ambrosia artemisiifolia is spreading in northern Europe due to climate change. The pollen are considered highly allergenic and might trigger allergy symptoms at much lower concentrations than e.g. grass or birch pollen. This study aims to determine threshold concentrations for ragweed and birch pollen in patients with seasonal allergic rhinitis. Participants will be exposed in an allergen challenge chamber that was technically modified to maintain very low and stable pollen concentrations for several hours. The study design is adaptive, where the pollen concentrations are escalated or de-escalated based on interim analysis of resulting allergic symptoms.
Status | Recruiting |
Enrollment | 18 |
Est. completion date | December 31, 2023 |
Est. primary completion date | December 31, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: 1. Able and willing to give written informed consent. 2. Male and female subjects, aged 18-65 years. Women will be considered for inclusion if they are: 1. Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing. 2. Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal, with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit). 3. Of childbearing potential and using a highly effective birth control during the entire study as described in section 8.2. 3. Body mass index between 18 and 35 kg/m2. 4. History of seasonal allergic rhinitis to ragweed (July to September) or birch pollen (March to May). 5. Positive skin prick test response (positive wheal diameter reaction of = 3mm) for Ambrosia artemisiifolia or Betula pendula at screening or within 12 months prior to screening visit. 6. Subject has a serum specific IgE level (= 0.7 kU/L) to Ambrosia artemisiifolia or Betula pendula at screening or within the past 12 months (record required). 7. Normal lung function (FEV1 = 80% pred. and FEV1/FVC = LLN) at screening. If subject fails to meet criteria, assessment may be repeated 2 additional times. 8. TNSS of 0 prior to entering the ACC at all exposures. 9. Mild to moderate level of rhinitis symptoms in the screening challenge to ragweed or birch, defined as a mean TNSS between 1 to 8 after the 4-hour ACC and a TNSS continuously > 0 after 40 minutes. Exclusion Criteria: 1. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function or ECG at screening visit , which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study. 2. Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis). 3. Subjects with concomitant allergies to seasonal aeroallergens (i.e., grass, trees, weeds, rye; defined as IgE = 3.5 kU/L within the last 12 months prior to screening) which are anticipated to be or become active during study participation. 4. Subjects with a symptomatic concomitant allergy to an animal dander being exposed during study participation. 5. Subjects with a symptomatic house dust mite allergy. 6. Symptoms of a respiratory tract infection within 3 days prior to screening. Subjects may be re-screened if they have been asymptomatic for at least 3 days. 7. Asthma requiring more than Step 1 medication according to GINA guidelines (Global Initiative for Asthma Management and Prevention, 2021). Asthmatic subjects taking ICS plus long-acting bronchodilator as needed according to Step 1 must to be switched to salbutamol as needed during study participation. 8. Intake of prohibited medication (refer to Section 9.2). 9. Smokers who are unable to refrain from smoking within 1 hr prior to and during visits. 10. Anatomical nasal abnormalities, pronounced nasal septum deviation or nasal polyps blocking nasal air flow on examination or recent nasal surgery. 11. Participation in a clinical trial with a medicinal product or medical device 30 days prior to Visit 1. 12. History of drug or alcohol abuse in the past 12 months. 13. Specific Immunotherapy (SIT) against birch or ragweed within 5 years prior to the study. 14. Risk of non-compliance with study procedures. 15. Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study. |
Country | Name | City | State |
---|---|---|---|
Germany | Fraunhofer Institute for Toxicology and Experimental Medicine | Hanover | Lower Saxony |
Lead Sponsor | Collaborator |
---|---|
Fraunhofer-Institute of Toxicology and Experimental Medicine |
Germany,
Buters J, Alberternst B, Nawrath S, Wimmer M, Traidl-Hoffmann C, Starfinger U, Behrendt H, Schmidt-Weber C, Bergmann KC. Ambrosia artemisiifolia (ragweed) in Germany - current presence, allergological relevance and containment procedures. Allergo J Int. 2015;24:108-120. doi: 10.1007/s40629-015-0060-6. Epub 2015 Jul 11. — View Citation
Gaudeul M, Giraud T, Kiss L, Shykoff JA. Nuclear and chloroplast microsatellites show multiple introductions in the worldwide invasion history of common ragweed, Ambrosia artemisiifolia. PLoS One. 2011 Mar 10;6(3):e17658. doi: 10.1371/journal.pone.0017658. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Measuring changes in fractioned exhaled nitric oxide before and after allergen challenges | Changes in nasal fractionated exhaled nitric oxide (FeNO) after challenge with ragweed and birch pollen compared to pre challenge nasal FeNO and placebo challenge | Day 1, Day 7, Day 14, Day 21, Day 28 (at least 3 exposure visits, maximum 5 exposure visits) | |
Other | Measuring changes in proinflammatory biomarkers before and after allergen challenges | Changes in inflammatory biomarkers such as histamine, eotaxin, IL-4, IL-5, IL-6, IL-13, TNF-a and MIP-1ß after challenge with ragweed and birch pollen compared to pre challenge and placebo measurements from nasal filter papers | Day 1, Day 2; Day 7, Day 8; Day 14, Day 15; Day 21, 22; Day 28, 29 (at least 3 exposure visits, maximum 5 exposure visits) | |
Other | Measuring changes in proinflammatory cells before and after allergen challenges | Changes in concentration of eosinophil and neutrophil granulocytes, macrophages, lymphocytes and monocytes after challenge with increasing cumulative exposures to ragweed and birch pollen compared to pre challenge and placebo measurements from nasal lavage | Day 1, Day 2; Day 7, Day 8; Day 14, Day 15; Day 21, 22; Day 28, 29 (at least 3 exposure visits, maximum 5 exposure visits) | |
Other | Measuring changes in basophil surface antigen expression under varying pollen concentrations in vitro | CD63 (%) and CD203c (median fluorescence intensity) expression on whole blood basophils after stimulation with increasing concentrations of ragweed or birch major allergens compared to negative control | Screening visit | |
Other | Measrung neutrophil migration under varying pollen major allergens concentrations in vitro | Neutrophil migration (% above basal migration) towards increasing concentrations of ragweed or birch major allergens compared to negative control | Screening visit | |
Primary | Threshold concentrations for ragweed and birch pollen | Changes in mean Total Nasal Symptom Score (TNSS) of 140 to 240 minutes, nasal secretion, and peak nasal inspiratory flow (PNIF) after challenge with ragweed and birch pollen compared to placebo challenge | Day 1, Day 7, Day 14, Day 21, Day 28 (at least 3 exposure visits, maximum 5 exposure visits) | |
Secondary | Determining allergenic potency of ragweed compared to birch pollen | Mean TNSS of 140 to 240 minutes after challenge with ragweed pollen compared to birch pollen | Day 1, Day 7, Day 14, Day 21, Day 28 (at least 3 exposure visits, maximum 5 exposure visits) | |
Secondary | Basophil activation under varying pollen concentrations in vitro | CD63 expression (%) on whole blood basophils after stimulation with increasing concentrations of ragweed or birch pollen compared to negative control | Screening visit | |
Secondary | Neutrophil migration under varying pollen concentrations in vitro | Neutrophil migration (% above basal migration) towards increasing concentrations of ragweed or birch pollen compared to negative control | Screening visit |
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